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Meng-Dan Zhao,1 Jun-Qin Li,2 Feng-Ying Chen,1 Wei Dong,3 Li-Juan Wen,4 Wei-Dong Fei,1 Xiao Zhang,1 Pei-Lei Yang,1 Xin-Mei Zhang,2 Cai-Hong Zheng1 1Department of Pharmacy, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, People’s Republic of China; 2Department of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, People’s Republic of China; 3Department of Neurology, The Affiliated Yangming Hospital of Ningbo University, Yuyao People’s Hospital of Zhejiang Province, Yuyao 315400, Zhejiang, People’s Republic of China; 4Institute of Pharmaceutics, College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, People’s Republic of ChinaCorrespondence: Xin-Mei Zhang; Cai-Hong Zheng Email zhangxinm@zju.edu.cn; chzheng@zju.edu.cnBackground: Ovarian cancer is a common malignancy in the female reproductive system with a high mortality rate. The most important reason is multidrug resistance (MDR) of cancer chemotherapy. To reduce side effects, reverse resistance and improve efficacy for the treatment of ovarian cancer, a “core-shell” polymeric nanoparticle-mediated curcumin and paclitaxel co-delivery platform was designed.Methods: Nuclear magnetic resonance confirmed the successful grafting of polyethylenimine (PEI) and stearic acid (SA) (PEI-SA), which is designed as a mother core for transport carrier. Then, PEI-SA was modified with hyaluronic acid (HA) and physicochemical properties were examined. To understand the regulatory mechanism of resistance and measure the anti-tumor efficacy of the treatments, cytotoxicity assay, cellular uptake, P-glycoprotein (P-gp) expression and migration experiment of ovarian cancer cells were performed. In addition, adverse reactions of nanoformulation to the reproductive system were examined.Results: HA-modified drug-loaded PEI-SA had a narrow size of about 189 nm in diameters, and the particle size was suitable for endocytosis. The nanocarrier could target specifically to CD44 receptor on the ovarian cancer cell membrane. Co-delivery of curcumin and paclitaxel by the nanocarriers exerts synergistic anti-ovarian cancer effects on chemosensitive human ovarian cancer cells (SKOV3) and multi-drug resistant variant (SKOV3-TR30) in vitro, and it also shows a good anti-tumor effect in ovarian tumor-bearing nude mice. The mechanism of reversing drug resistance may be that the nanoparticles inhibit the efflux of P-gp, inhibit the migration of tumor cells, and curcumin synergistically reverses the resistance of PTX to increase antitumor activity. It is worth noting that the treatment did not cause significant toxicity to the uterus and ovaries with the observation of macroscopic and microscopic.Conclusion: This special structure of targeting nanoparticles co-delivery with the curcumin and paclitaxel can increase the anti-tumor efficacy without increasing the adverse reactions as a promising strategy for therapy ovarian cancer.Keywords: co-delivery, curcumin, reverse resistance, paclitaxel, ovarian cancer, adverse reactions

Objectives: The guidelines recommend fractional flow reserve-guided coronary artery bypass grafting (CABG) during primary valve surgery without evidence. Quantitative flow ratio (QFR) is a novel coronary angiography (CAG)-based fractional flow reserve measurement. We aimed to compare the early clinical outcomes between QFR-guided and CAG-guided CABG in these patients. Methods: This observational study screened all 2081 patients admitted to our institution for elective primary mitral and/or aortic valve surgery from January 2017 to September 2020. Of them, all 188 patients with comorbid coronary artery lesions (visual estimated stenosis ≥50%) were included. Sixty-nine patients with QFR analysis received bypasses only for lesions with QFR ≤0.80 (QFR-guided group). The remaining 119 patients without QFR analysis received bypasses for all stenosis ≥50% (CAG-guided group). Propensity overlap weighting was used to neutralize the intergroup imbalance. The primary end point was major adverse cardiovascular events. Results: After propensity score weighting, the baseline characteristics were comparable. Concomitant coronary artery bypass grafting was performed 58.1% versus 100% in the QFR-guided and CAG-guided groups, respectively. The mean number of grafts was significantly lower in QFR-guided group than in the CAG-guided group (0.9 ± 0.7 vs 1.6 ± 0.5 [P

Meng-Dan Zhao,1 Jin-Lin Cheng,2 Jing-Jing Yan,1 Feng-Ying Chen,1 Jian-Zhong Sheng,3 Dong-Li Sun,1 Jian Chen,4 Jing Miao,4 Run-Ju Zhang,1 Cai-Hong Zheng,1 He-Feng Huang1,5 1Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, 3Department of Pathophysiology, School of Medicine, 4The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 5International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Abstract: To identify a new drug candidate for treating endometriosis which has fewer side effects, a new polymeric nanoparticle gene delivery system consisting of polyethylenimine-grafted chitosan oligosaccharide (CSO-PEI) with hyaluronic acid (HA) and small interfering RNA (siRNA) was designed. There was no obvious difference in sizes observed between (CSO-PEI/siRNA)HA and CSO-PEI/siRNA, but the fluorescence accumulation in the endometriotic lesion was more significant for (CSO-PEI/siRNA)HA compared with CSO-PEI/siRNA due to the specific binding of HA to CD44. In addition, the (CSO-PEI/siRNA)HA nanoparticle gene therapy significantly decreased the endometriotic lesion sizes with atrophy and degeneration of the ectopic endometrium. The epithelial cells of ectopic endometrium from rat models of endometriosis showed a significantly lower CD44 expression than control after treatment with (CSO-PEI/siRNA)HA. Furthermore, observation under an electron microscope showed no obvious toxic effect on the reproductive organs. Therefore, (CSO-PEI/siRNA)HA gene delivery system can be used as an effective method for the treatment of endometriosis. Keywords: chitosan-PEI, hyaluronic acid, AQP2-siRNA, endometriosis, targeted therapy

Background: There is no consensus on optimal time points or systolic blood pressure (SBP) ranges for calculating SBP time in target range (TTR). Objectives: The purpose of this study was to examine the association between various SBP TTR metrics and long-term major adverse cardiovascular events (MACEs). Methods: This post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) included participants with complete SBP records and excluded those with events in the initial 2 years. SBP TTR indices were calculated using 3 distinct time points and 3 SBP ranges. The SBP TTR index was the percentage of BP segments within the target SBP ranges. MACE, a composite of heart attack, stroke, heart failure, and cardiovascular death, was the primary outcome. Results: The study included 7,134 participants, of which 280 had a MACE. The median follow-up was 3.91 years. The SBP TTR 110-140 mm Hg in the initial 3 months (3-month TTR 110-140) had the optimal association with incident MACEs (HR per SD increase: 0.898 [95% CI: 0.788-1.022], relative informativeness = 24,398%). Furthermore, a cutoff value of 0.65 for 3-month TTR 110 to 140 index was identified by threshold saturation analysis and used to evaluate early SBP control. No difference in MACE was seen between different mean SBP subgroups in those with good early control (3-month TTR >0.65) (P = 0.88), but in those with poor early control (3-month TTR ≤0.65), a higher mean SBP of 130 to 140 mm Hg was related to increased MACEs risk (P = 0.019). Conclusions: In nondiabetic hypertensive patients, the 3-month TTR 110 to 140 mm Hg index was independently associated with 2-year MACEs. A cutoff of TTR index as 0.65 indicated that the patient was within BP target range 65% of the time, combined with mean SBP, could potentially be used as a metric for early control stability and late cardiovascular risks. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062)

Feng-Ying Chen,1 Jing-Jing Yan,1 Han-Xi Yi,2 Fu-Qiang Hu,2 Yong-Zhong Du,2 Hong Yuan,2 Jian You,2 Meng-Dan Zhao1 1Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2College of Pharmaceutical Science, Zhejiang University, Hangzhou, People’s Republic of China Abstract: Nowadays, a real challenge in cancer therapy is to design drug delivery systems that can achieve high concentrations of drugs at the target site for improved therapeutic effect with reduced side effects. In this research, we designed and synthesized a homing peptide-(TNYLFSPNGPIA, TNYL) modified chitosan-g-stearate (CS) polymer micelle (named T-CS) for targeting delivery. The peptide displayed specific binding affinity to EphB4 which is a member of the Eph family of receptor tyrosine protein kinases. The amphiphilic polymer T-CS can gather into micelles by themselves in an aqueous environment with a low critical micelle concentration value (91.2 µg/L) and nano-scaled size (82.1±2.8 nm). The drug encapsulation efficiency reached 86.43% after loading the hydrophobic drug doxorubicin (DOX). The cytotoxicity of T-CS/DOX against SKOV3 cells was enhanced by approximately 2.3-fold when compared with CS/DOX. The quantitative and qualitative analysis for cellular uptake indicated that TNYL modification can markedly increase cellular internalization in the EphB4-overexpressing SKOV3 cell line, especially with a short incubation time. It is interesting that relatively higher uptake of the T-CS/DOX micelles by SKOV3 cells (positive-EphB4) than A549 cells (negative-EphB4) was observed when the two cells were co-incubated. Furthermore, in vivo distribution experiment using a bilateral-tumor model showed that there was more fluorescence accumulation in the SKOV3 tumor than in the A549 tumor over the whole experiment. These results suggest that TNYL-modified CS micelles may be promising drug carriers as targeting therapy for the EphB4-overexpressing tumor. Keywords: chitosan-g-stearate, polymeric micelles, TNYL, active targeting, antitumor activity

Objective: To explore the diagnostic value of real-time shear wave elastography (SWE) in hepatic hemangioma (ANGI) and hepatocellular carcinoma (HCC). Methods: A total of 88 patients diagnosed with angiosarcoma (ANGI) or hepatocellular carcinoma (HCC) in our department from February 2019 to February 2020 were included in this study. These patients were assigned to two groups based on pathological diagnosis: the ANGI group (n = 42) and the HCC group (n = 46). All patients underwent SWE examination, and the clinical efficacy was analyzed by comparing the average value of Young's modulus of the two groups and plotting the receiver operator characteristic (ROC) curve. Results: There was no significant difference in lesion diameter between ANGI and HCC patients (P > 0.05). The ANGI group exhibited a significantly higher average Young's modulus for both the lesions and the adjacent liver tissues compared to the HCC group (P < 0.001); The area under the curve (AUC) of the average value of Young’s modulus of the lesion to ANGI and HCC was 0.875 (95% CI = 0.795-0.955). Conclusion: SWE demonstrates high diagnostic accuracy in distinguishing ANGI from HCC, providing valuable clinical evidence for differentiating between the two diseases.

Primary cardiac angiosarcoma is a rare, aggressive malignancy that commonly metastasizes to various organs. The presenting symptoms are typically nonspecific, so a comprehensive examination is required to confirm the diagnosis promptly. This case report describes the presentation of an older patient with a history of neoplasms. Echocardiography and biopsy were performed, but despite surgical intervention to resect a large right atrial mass, the patient died. A final diagnosis of primary angiosarcoma was made based on the resected specimen.

Background: Hip dislocation represents a significant complication encountered following hip arthroplasty procedures. In this investigation, we conducted a comparative analysis of the biomechanical characteristics exhibited by the piriformis and the conjoined tendon after total hip arthroplasty (THA) via the direct anterior approach (DAA), utilizing cadaveric specimens. The objective is to ascertain the relative significance of the piriformis muscle and the conjoined tendon in mitigating hip dislocation. Methods: A total of 16 hip joints from 8 freshly frozen cadavers were selected and stratified into 2 groups: the piriformis tendon (PT) group and the conjoined tendon (CT) group. Following THA via the DAA, measurements were taken to record the torque required to induce hip dislocation under various conditions. Torque readings were obtained with the tendon in its intact state (intact group) and after preservation or reconstruction of either the PT or the CT. Results: The torques of anterior and posterior dislocation in PT group were 22.24 ± 4.53 N.m and 30.7 ± 15.5 N.m following tendon severed, and 20.04 ± 2.67 N.m and 17.5 ± 6.7 N.m following reconstruction. There were no differences compared to the intact group. The torque decreased in the CT group after CT was severed with the torques dropping from 31.2 ± 7.6 N.m to 8.18 ± 2.6 N.m (P < .0001) for anterior dislocation, and from 34.9 ± 8.3 N.m to 9.8 ± 2.8 N.m (P < .0001) for posterior dislocation. Following reconstruction, the torque required for dislocation significantly increased (P < .0001). Conclusions: This study underscores the preeminent role of the CT in ensuring hip stability following THA via DAA, highlighting the cruciality of its preservation and reconstruction during surgical interventions.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is prevalent and increasingly reported. Its diagnosis traditionally follows the Kidney Disease: Improving Global Outcomes (KDIGO) AKI criteria. However, little evidence supports its appropriateness for cardiac surgery patients, particularly regarding the subtle serum creatinine change (ΔSCr) that defines mild AKI. Objectives: The purpose of the study was to investigate the ΔSCr threshold specific to CSA-AKI and compare its impact on CSA-AKI incidence and prognosis with the KDIGO AKI criteria threshold. Methods: A 10-year coronary surgery cohort with serial perioperative SCr measurements was retrospectively analyzed. The relationship and prognostically significant threshold of 48-hour absolute ΔSCr with 30-day mortality were explored using multivariate restricted cubic spline analysis and receiver-operating characteristic curve analysis. AKI incidence and prognostic value were compared between adopting the KDIGO or new thresholds. Results: Among 37,706 patients, 20,290 (53.8%) developed KDIGO-defined AKI. For stage-1 AKI (18,835, 49.9%), the majority (75.2%) were solely attributed to the KDIGO absolute criterion (48-hour ΔSCr ≥0.3 mg/dL). The 48-hour ΔSCr threshold associated with an adjusted odds ratio ≥1.00 for 30-day mortality was 0.549 mg/dL. A similar threshold (0.553 mg/dL) was also identified based on the Youden index cutoff. Applying the 0.55 mg/dL threshold to define stage 1 CSA-AKI, the overall and stage-1 CSA-AKI incidence decreased to 21.0% and 17.2%, with 27.7% of the stage-1 CSA-AKI solely attributed to the new criterion. The prognostic value for AKI defined by this new threshold was significantly higher than the KDIGO criteria. Conclusions: A cardiac surgery-specific ΔSCr threshold in defining AKI was notably higher compared with the current general AKI definition.

Purpose: To compare the usefulness of microperimetry and static automated perimetry in patients with retinitis pigmentosa (RP), using macular anatomical metrics as a reference. Design: Prospective observational study. Participants: Forty-eight eyes of 48 patients with RP in Kyushu University Hospital who underwent microperimetry-3 (MP-3) and Humphrey Field Analyzer (HFA) 10-2 testing ≥3 times during ≥2 years were included. Methods: Macular anatomy (ellipsoid zone [EZ] length) was assessed by OCT, and macular function was assessed by MP-3 (mean retinal sensitivity at radii 2°, 4°, and 8°) and HFA10-2 program (mean retinal sensitivity at radii 2°, 4°, and 8°). Correlations between functional and anatomical parameters were analyzed cross sectionally at baseline and longitudinally by comparing the rate of progression. Main Outcome Measures: Correlation coefficients between anatomical and functional metrics. Results: The mean age at baseline was 50.1 ± 12.3 years, and the mean follow-up period was 2.8 ± 0.7 years. At baseline, EZ length was significantly correlated with MP-3 mean retinal sensitivity at radii 2°, 4°, and 8° (Spearman’s ρ = 0.65, 0.84, 0.89; all P

Background Abnormalities in mitochondrial structure or function are closely related to the development of malignant tumors. Mitochondrial metabolic reprogramming provides precursor substances and energy for the vital activities of tumor cells, so that cancer cells can rapidly adapt to the unfavorable environment of hypoxia and nutrient deficiency. Mitochondria can enable tumor cells to gain the ability to proliferate, escape immune responses, and develop drug resistance by altering constitutive junctions, oxidative phosphorylation, oxidative stress, and mitochondrial subcellular relocalization. This greatly reduces the rate of effective clinical control of tumors. Purpose Explore the major role of mitochondria in cancer, as well as targeted mitochondrial therapies and mitochondria-associated markers. Conclusions This review provides a comprehensive analysis of the various aspects of mitochondrial aberrations and addresses drugs that target mitochondrial therapy, providing a basis for clinical mitochondria-targeted anti-tumor therapy.

Lu Cao,1 Ping-Guo Duan,1 Xi-Lei Li,1 Feng-Lai Yuan,3 Ming-Dong Zhao,2 Wu Che,1 Hui-Ren Wang,1 Jian Dong11Department of Orthopedic Surgery, Zhongshan Hospital, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, China; 2Department of Orthopedic Surgery, Jinshan Hospital, Fudan University, Shanghai, China; 3Affiliated Third Hospital of Nantong University, Wuxi, ChinaPurpose: The aim of this study was to investigate the biomechanical stability provided by a novel, polylactic acid/nano-sized, β-tricalcium phosphate, bioabsorbable, self-retaining cervical fusion cage (BCFC).Methods: Quasistatic nonconstraining torques (maximum 1.5 NM) induced flexion, extension, lateral bending (±1.5 NM), and axial rotation (±1.5 NM) on 32 sheep cervical spines (C2–C5). The motion segment C3–C4 was first tested intact; the following groups were tested after complete discectomy: autologous tricortical iliac crest bone graft, Medtronic–Wego polyetheretherketone (PEEK) cage, Solis PEEK cage, and BCFC. The autologous bone graft group was tested with an anterior plate. The mean range of motion (ROM) was calculated from the load-displacement curves.Results: BCFC significantly decreased ROM in lateral bending and axial rotation compared to other implants, and no significant difference in ROM between two types of PEEK cages and BCFC could be observed in flexion and extension. Anterior cervical plate (ACP) significantly decreased ROM in flexion and extension, but no significant difference in ROM between BCFC and bone graft plus ACP could be determined in lateral bending and axial rotation.Conclusion: The BCFC device showed better stability to autologous tricortical iliac crest bone graft and PEEK cages in single-level anterior cervical discectomy and fusion models and thus may be a potential alternative to the current PEEK cages.Keywords: biomechanics, cervical spine, cages, bioabsorbable, sheep

Introduction Breast cancer is one of the most prevalent types of cancer and a leading cause of cancer-related death among females worldwide. Anoikis, a specific type of apoptosis that is triggered by the loss of anchoring between cells and the native extracellular matrix, plays a vital role in cancer invasion and metastasis. However, studies that focus on the prognostic values of anoikis-related genes (ARGs) in breast cancer are scarce. Methods Gene expression data were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Five anoikis-related signatures (ARS) were selected from ARGs through univariate Cox regression analysis, LASSO regression analysis, and multivariate Cox regression analysis. Subsequently, an ARGs risk score model was established, and breast cancer patients were divided into high and low risk groups. The correlation between risk groups and overall survival (OS), tumor mutation burden (TMB), tumor microenvironment (TME), stemness, and drug sensitivity were analyzed. Moreover, RT-qPCR was performed to verify the gene expression levels of the five ARS in breast cancer tissues. Furthermore, a nomogram model was constructed based on ARGs risk score and clinicopathological factors. Results A novel ARGs risk score model was constructed based on five ARS (CEMIP, LAMB3, CD24, PTK6, and PLK1), and breast cancer patients were divided into high and low risk groups. Correlation analysis showed that the high and low risk groups had different OS, TMB, TME, stemness, and drug sensitivity. Both the ARGs risk score model and the nomogram showed promising prognosis predictive value in breast cancer. Conclusion ARS could be used as promising biomarkers for breast cancer prognosis predication and treatment options selection.

Background: Thrombolytic therapy is essential for acute ischemic stroke (AIS) management but poses a risk of hemorrhagic transformation (HT), necessitating accurate prediction to optimize patient care. Methods: A comprehensive search was conducted across PubMed, Web of Science, Scopus, Embase, and Google Scholar, covering studies from inception until July 10, 2024. Studies were included if they used machine learning (ML) or deep learning algorithms to predict HT in AIS patients treated with thrombolysis. Exclusion criteria included studies involving endovascular treatments and those not evaluating model effectiveness. Data extraction and quality assessment were performed following PRISMA guidelines and using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Risk of Bias Assessment Tool (PROBAST) tools. Results: Out of 1943 identified records, 12 studies were included in the final analysis, encompassing 18 007 AIS patients who received thrombolytic therapy. The ML models demonstrated high predictive performance, with pooled area under the curve (AUC) values ranging from 0.79 to 0.95. Specifically, XGBoost models achieved AUCs of up to 0.953 and Artificial Neural Network (ANN) models reached up to 0.942. Sensitivity and specificity varied significantly, with the highest sensitivity at 0.90 and specificity at 0.99. Significant predictors of HT included age, glucose levels, NIH Stroke Scale (NIHSS) score, systolic and diastolic blood pressure, and radiomic features. Despite these promising results, methodological disparities and limited external validation highlighted the need for standardized reporting and further rigorous testing. Conclusion: ML techniques, especially XGBoost and ANN, show great promise in predicting HT following thrombolysis in AIS patients, enhancing risk stratification and clinical decision-making. Future research should focus on prospective study designs, standardized reporting, and integrating ML assessments into clinical workflows to improve AIS management and patient outcomes.

Background Recently, the effect of Lipoprotein(a) [Lp(a)] on thrombogenesis has aroused great interest, while inflammation has been reported to modify the Lp(a)-associated risks through an unidentified mechanism. Purpose This study aimed to evaluate the association between platelet reactivity with Lp(a) and high-sensitivity C-reactive protein (hs-CRP) levels in percutaneous intervention (PCI) patients treated with clopidogrel. Methods Data were collected from 10,724 consecutive PCI patients throughout the year 2013 in Fuwai Hospital. High on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) were defined as thrombelastography (TEG) maximum amplitude of adenosine diphosphate-induced platelet (MA ADP ) > 47 mm and

This study aimed to evaluate the safety and efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) and stenting for treating acute iliofemoral deep venous thrombosis (DVT) combined with iliac vein compression syndrome (IVCS), and to identify the predictors of stent restenosis. Patients with acute proximal DVT combined with IVCS underwent PCDT and stenting from January 2017 to December 2022 were enrolled. Primary and secondary patency were assessed by duplex ultrasound (DUS). The morbidity of postthrombotic syndrome (PTS) was assessed by the Villalta score. Risk factors for stent restenosis were assessed using univariate and multivariate Cox regression models. Total of 254 patients were included. The mean follow-up time was 36.06 ± 17.66 months. The primary patency rates at 1 year, 3 years, and 5 years were 92.5%±1.7%, 85.4%±2.4%, and 82.4%±2.9%, respectively. The incidence of stent restenosis was 14.2%. Discontinuation of anticoagulants within one year [hazard ratio (HR) = 5.03; P = .048] was the factor associated with acute in-stent thrombosis. Previous DVT history (HR =2.29; P = .037) and stent placement across the inguinal ligament (HR =6.70; P

Elevated circulating D-dimer levels have been shown to be a predictor of in-hospital mortality in a variety of diseases; however, the relationship between D-dimer and the in-hospital prognosis of non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. This retrospective study included 662 non-diabetic patients with NSTEMI. Independent risk factors were identified by multivariate analyses, and the receiver operating characteristic (ROC) curve analyses were performed to compare the predictive value of D-dimer, albumin (ALB), and D-dimer to albumin ratio (DAR) for in-hospital death in NSTEMI. Logistic regression model with restricted cubic spline (RCS) was used to further explore the linear or nonlinear relationship between D-dimer and the risk of death. In-hospital mortality occurred in 38 (5.7%) patients. Multivariate analysis showed that D-dimer (per increase of 500 ng) was identified as an independent predictor for in-hospital mortality in non-diabetic patients with NSTEMI (OR = 1.19, 95% CI: 1.03–1.40, P = 0.036). D-dimer demonstrated good predictive performance for in-hospital mortality with an area under the ROC curve (AUC) value of 0.75 (95% CI: 0.66–0.83), and there was no significant difference in the predictive ability of D-dimer, ALB (AUC = 0.70, 95% CI: 0.61–0.79) and DAR (AUC = 0.75, 95% CI: 0.66–0.84). In addition, RCS analysis showed a linear relationship between D-dimer and the risk of in-hospital mortality (P for nonlinear = 0.747). D-dimer can be used as a simple, reliable and valuable biomarker for predicting in-hospital mortality in non-diabetic patients with NSTEMI and is linearly associated with the risk of death.

Disseminated intravascular coagulation (DIC) poses a high mortality risk, yet its exact impact remains contentious. This study investigates DIC's association with mortality in individuals with sepsis, emphasizing multiple organ function. Using data from the Peking University People's Hospital Investigation on Sepsis-Induced Coagulopathy database, we categorized patients into DIC and non-DIC groups based on DIC scores within 24 h of ICU admission (< 5 cutoff). ICU mortality was the main outcome. Initial data comparison preceded logistic regression analysis of mortality factors post-propensity score matching (PSM). Employing mediation analysis estimated direct and indirect associations. Of 549 participants, 131 were in the DIC group, with the remaining 418 in the non-DIC group. Following baseline characteristic presentation, PSM was conducted, revealing significantly higher nonplatelet sequential organ failure assessment (nonplt-SOFA) scores (6.3 ± 2.7 vs 5.0 ± 2.5, P

Objectives Accurate survival predictions and early interventional therapy are crucial for people with clear cell renal cell carcinoma (ccRCC). Methods In this retrospective study, we identified differentially expressed immune-related (DE-IRGs) and oncogenic (DE-OGs) genes from The Cancer Genome Atlas (TCGA) dataset to construct a prognostic risk model using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. We compared the immunogenomic characterization between the high- and low-risk patients in the TCGA and the PUCH cohort, including the immune cell infiltration level, immune score, immune checkpoint, and T-effector cell- and interferon (IFN)-γ-related gene expression. Results A prognostic risk model was constructed based on 9 DE-IRGs and 3 DE-OGs and validated in the training and testing TCGA datasets. The high-risk group exhibited significantly poor overall survival compared with the low-risk group in the training ( P < 0.0001), testing ( P = 0.016), and total ( P < 0.0001) datasets. The prognostic risk model provided accurate predictive value for ccRCC prognosis in all datasets. Decision curve analysis revealed that the nomogram showed the best net benefit for the 1-, 3-, and 5-year risk predictions. Immunogenomic analyses of the TCGA and PUCH cohorts showed higher immune cell infiltration levels, immune scores, immune checkpoint, and T-effector cell- and IFN-γ-related cytotoxic gene expression in the high-risk group than in the low-risk group. Conclusion The 12-gene prognostic risk model can reliably predict overall survival outcomes and is strongly associated with the tumor immune microenvironment of ccRCC.

Spinal cord astrocytoma (SCA) is a rare subtype of astrocytoma, posing challenges in diagnosis and treatment. Low-grade SCA can achieve long-term survival solely through surgery, while high-grade has a disappointing prognosis even with comprehensive treatment. Diagnostic criteria and standard treatment of intracranial astrocytoma have shown obvious limitations in SCA. Research on the molecular mechanism in SCA is lagging far behind that on intracranial astrocytoma. In recent years, huge breakthroughs have been made in molecular pathology of astrocytoma, and novel techniques have emerged, including DNA methylation analysis and radiomics. These advances are now making it possible to provide a precise diagnosis and develop corresponding treatment strategies in SCA. Our aim is to review the current status of diagnosis and treatment of SCA, and summarize the latest research advancement, including tumor subtype, molecular characteristics, diagnostic technology, and potential therapy strategies, thus deepening our understanding of this uncommon tumor type and providing guidance for accurate diagnosis and treatment.

Background/Objective: Cribriform-morular thyroid carcinoma (CMTC) was considered a variant of papillary thyroid carcinoma (PTC) but is a separate entity in the 2022 World Health Organization classification. CMTC has an association with familial adenomatous polyposis (FAP). Our objective is to report a case of CMTC who was subsequently diagnosed with FAP, to highlight these associated entities and implications for management. Case Report: A 15-year-old female with a history of iron-deficiency anemia and alpha-gal syndrome presented with several years of goiter and dysphagia. She also noted unintentional weight loss, abdominal pain, melena and hematochezia, and symptomatic anemia. Physical examination was significant for multiple thyroid nodules. Laboratory results revealed normal thyroid function and iron deficiency. Multiple nodules were visualized on thyroid ultrasound, and fine needle aspiration biopsy was consistent with PTC. Total thyroidectomy was performed with a revised diagnosis of multifocal CMTC, with administration of adjuvant radioactive iodine due to persistent disease. Genetic testing confirmed FAP and she was referred for upper endoscopy, colonoscopy, and an evaluation for colectomy. Discussion: There are no best practice guidelines for management of CMTC. Management of CMTC is guided by FAP status; sporadic cases can be managed with hemithyroidectomy, while FAP-associated cases are better managed with total thyroidectomy. Recurrence is usually managed with surgical resection. The decision to treat with adjuvant radioactive iodine is often extrapolated from management of classic PTC. Conclusion: Thyroid carcinoma in the setting of extensive family history of colorectal carcinoma should arouse suspicion for CMTC. Patients with CMTC should receive a referral for colonoscopy and genetic testing for FAP.

Objective The purpose of this study was to apply contemporary consensus criteria developed by the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology to the evaluation of aortic pathology, with the expectation that the additional pathologic information may enhance the understanding and management of aortic diseases. Methods A scoring system was applied to ascending aortic specimens from 42 patients with heritable thoracic aortic disease and known genetic variations and from 86 patients from a single year, including patients with known genetic variations (n = 12) and patients with sporadic disease (n = 74). Results The various types of lesions of medial degeneration and the overall severity of medial degeneration overlapped considerably between those patients with heritable disease and those with sporadic disease; however, patients with heritable thoracic aortic disease had significantly more overall medial degeneration (P = .004) and higher levels of elastic fiber fragmentation (P = .03) and mucoid extracellular matrix accumulation (P = .04) than patients with sporadic thoracic aortic disease. Heritable thoracic aortic disease with known genetic variation was more prevalent in women than in men (27.2% vs 9.8%; P = .04), and women had more severe medial degeneration than men (P = .04). Medial degeneration scores were significantly lower for patients with bicuspid aortic valves than for patients with tricuspid aortic valves (P = .03). Conclusion The study’s findings indicate considerable overlap in the pattern, extent, and severity of medial degeneration between sporadic and hereditary types of thoracic aortic disease. This finding suggests that histopathologic medial degeneration represents the final common outcome of diverse pathogenetic factors and mechanisms.

Background:. Although the transversus abdominal plane (TAP) block is commonly used in abdominal surgery as part of enhanced recovery after surgery pathways, the quadratus lumborum (QL) block has been hypothesized as an effective alternative to the TAP block in some areas. This review evaluates the current literature, as it relates to the QL block in plastic and reconstructive surgery. Methods:. A systematic review using PubMed searched for all original, peer-reviewed articles, including the term “quadratus lumborum block.” In total, 509 articles were identified for review by two independent reviewers. Original articles evaluating the use of a QL block in any plastic surgery operation were included. Articles evaluating pediatric patients, animal trials, and the use of a QL block in any nonplastic surgery operation were excluded. Results:. Three articles met inclusion criteria. One trial demonstrated decreased subjective pain scores and total opioid use, whereas the second found no statistically significant difference. A case study described the use of a QL block for unilateral breast reconstruction with minimal opiate use and reduced pain scores postoperatively. Limitations include the limited number of studies and the heterogeneity in study type and design, making analysis difficult. Conclusions:. Despite its demonstrated efficacy in other surgical subspecialties, there are limited data evaluating the use of the QL block in plastic and reconstructive surgery. Additional research is needed to evaluate the role of the QL block in plastic surgery and how it compares to the more widely utilized TAP block.

Venous thromboembolism (VTE) is associated with high morbidity and mortality. Risk scores associated with VTE have been widely used in clinical practice. Among numerous scores published, those included in guidelines are usually typical risk scores which have been extensively validated and globally recognized. This review provides an updated overview of the risk scores associated with VTE endorsed by 3 guidelines which are highly recognized in the field of VTE including the European Society of Cardiology, American College of Chest Physicians, and American Society of Hematology, focusing on the development, modification, validation, and comparison of these scores, to provide a comprehensive and updated understanding of all the classic risk scores associated with VTE to medical readers including but not limited to cardiologists, pulmonologists, hematologists, intensivists, physicians, surgeons, and researchers. Although each score recommended by these guidelines was more or less validated, there may still be room for further improvement. It may still be necessary to seek simpler, more practical, and more universally applicable VTE-related risk scores in the future.

Background Labeled antibodies are excellent imaging agents in oncology to non-invasively visualize cancer-related antigens expression levels. However, tumor tracer uptake (TTU) of specific antibodies in-vivo may be inferior to non-specific IgG in some cases. Objectives To explore factors affecting labeled antibody visualization by PD-L1 specific and non-specific imaging of nude mouse tumors. Methods TTU was observed in RKO model on Cerenkov luminescence (CL) and near-infrared fluorescence (NIRF) imaging of radionuclide 131 I or NIRF dyes labeled Atezolizumab and IgG. A mixture of NIRF dyes labeled Atezolizumab and 131 I-labeled IgG was injected, and TTU was observed in the RKO and HCT8 model by NIRF/CL dual-modality in-situ imaging. TTU were observed by 131 I-labeled Atezolizumab and IgG in-vitro distribution. Results Labeled IgG concentrated more in tumors than Atezolizumab. NIRF/CL imaging in 24 to 168 h showed that TTU gradually decreased over time, which decreased more slowly on CL imaging compared to NIRF imaging. The distribution data in-vitro showed that TTU of 131 I-labeled IgG was higher than that of 131 I-labeled Atezolizumab at any time point. Conclusion Non-specific IgG may not be suitable as a control for Atezolizumab in comparing tumor PD-L1 expression in nude mice via labeled antibody optical imaging under certain circumstances.

Objectives Gastric cancer (GC) is one of the most prevalent malignancies worldwide, and early detection is crucial for improving patient survival rates. We aimed to identify immune infiltrating cell-related biomarkers in early gastric cancer (EGC) progression. Methods The GSE55696 and GSE130823 datasets with low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and EGC samples were downloaded from the Gene Expression Omnibus database to perform an observational study. Immune infiltration analysis was performed by single sample gene set enrichment analysis and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data. Weighted gene co-expression network analysis was used to explore the co-expression modules and genes, and further enrichment analysis was performed on these genes. A protein-protein interaction (PPI) network of these genes was constructed to identify biomarkers associated with EGC progression. Screened hub genes were validated by the rank sum test and reverse transcription quantitative polymerase chain reaction. Results Immune scores were significantly elevated in EGC samples compared to LGIN and HGIN samples. The green-yellow module exhibited the strongest correlation with both immune score and disease progression. The 87 genes within this module were associated with the chemokine signaling pathways, the PI3K-Akt signaling pathways, leukocyte transendothelial migration, and Ras signaling pathways. Through PPI network analysis, the hub genes identified were protein tyrosine phosphatase receptor-type C (PTPRC), pleckstrin, CD53, CD48, lymphocyte cytosolic protein 1 (LCP1), hematopoietic cell-specific Lyn substrate 1, IKAROS Family Zinc Finger 1, Bruton tyrosine kinase, and Vav guanine nucleotide exchange factor 1. Notably, CD48, LCP1, and PTPRC showed high expression levels in EGC samples, with the remaining hub genes demonstrating a similar expression trend. Conclusion This study identified 9 immune cell-related biomarkers that may be actively involved in the progression of EGC and serve as potential targets for GC diagnosis and treatment.

Introduction It is appealing to accurately predict postoperative delirium (POD) before surgeries. In this study, it was hypothesized that a novel electroencephalogram-derived index, the delirium index (DELi), could extract latent information regarding the predisposing factors of POD preoperatively. This study was aimed at developing a concise model that incorporated this DELi score to predict the early POD of elderly patients after hip surgeries. Materials and Methods Elderly patients scheduled for elective hip fracture surgeries were prospectively enrolled in a tertiary care hospital from November 2020 to June 2022. DELi scores and patient characteristics (age, sex, types of fracture and surgery, the time interval between fracture and surgery, cognitive function assessed using the Montreal Cognitive Assessment (MoCA), and frailty status assessed using the FRAIL scale) were collected preoperatively as candidate predictors. POD diagnosed using the confusion assessment method (CAM) was the outcome. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to select predictors. Then, these predictors were entered into a backward logistical regression analysis to develop a prediction model. Discrimination, calibration and clinical utility were validated using the bootstrapping method. Results All data (144 qualified patients of 170) were used for development. POD was observed in 71 patients (49.3%). Preoperative DELi scores predicted early POD (the area under the curve (AUC) = .786, 95% confidence interval (CI): .712, .860, in internal validation). A nomogram with MoCA, FRAIL scale and DELi score was constructed with excellent discrimination (AUC = .920, 95% CI: .876, .963, in internal validation), accredited calibration ( P = .733, Hosmer‒Lemeshow test), and a wide range of threshold probabilities (5% to 95%). Conclusions Preoperative DELi scores predicted the early POD of elderly patients after hip surgeries. A concise prediction model was developed and demonstrated excellent discrimination.

Objectives Circular RNAs (circRNAs) serve a crucial regulatory role in ovarian cancer (OC). Circular RNA ArfGAP with FG repeats 1 (circAGFG1) has been shown to be involved in promoting the progression of several cancers, containing triple-negative breast cancer, esophageal cancer and colorectal cancer. However, the function of circAGFG1 in OC is unclear. Methods Quantitative real-time reverse transcription PCR (RT-qPCR) was conducted to determine the expression levels of circAGFG1 and miR-409-3p. The proliferation and metastasis of cells were determined by colony formation assays, EdU assays, transwell assays and wound healing assays. In addition, a dual-luciferase reporter assay was performed to validate the mechanism between circAGFG1, miR-409-3p, and ZEB1. Results Our data suggested that circAGFG1 was significantly overexpressed in OC tissues compared to normal ovarian epithelial tissues. Overexpression of circAGFG1 was correlated with intraperitoneal metastasis, tumor recurrence and advanced stage. Additionally, circAGFG1 overexpression revealed a poor prognosis in OC patients. Knockdown of circAGFG1 suppressed the proliferation, invasion and migration of OC cells. Mechanistically, circAGFG1 acted as a sponge of miR-409-3p to enhance the expression level of zinc finger E-box binding homeobox 1 (ZEB1), thereby conferring OC cell proliferation, invasion and migration. Importantly, re-expression of ZEB1 effectively reversed the effects of circAGFG1 knockdown on OC cells. Conclusions In summary, our study indicated that circAGFG1 may act as a prognostic biomarker and potential therapeutic target for patients with OC.

Background. In organ transplantation, ischemia, and reperfusion injury (IRI) is considered as an inevitable event and the major contributor to graft failure. Ischemia-free liver transplantation (IFLT) is a novel transplant procedure that can prevent IRI and provide better transplant outcomes. However, a large animal model of IFLT has not been reported. Therefore, we develop a new, reproducible, and stable model of IFLT in pigs for investigating mechanisms of IFLT in IRI. Methods. Ten pigs were subjected to IFLT or conventional liver transplantation (CLT). Donor livers in IFLT underwent 6-h continuous normothermic machine perfusion (NMP) throughout graft procurement, preservation, and implantation, whereas livers in CLT were subjected to 6-h cold storage before implantation. The early reperfusion injury was compared between the 2 groups. Results. Continuous bile production, low lactate, and liver enzyme levels were observed during NMP in IFLT. All animals survived after liver transplantation. The posttransplant graft function was improved with IFLT when compared with CLT. Minimal histologic changes, fewer apoptotic hepatocytes, less sinusoidal endothelial cell injury, and proinflammatory cytokine (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) release after graft revascularization were documented in the IFLT group versus the CLT group. Conclusions. We report that the concept of IFLT is achievable in pigs. This innovation provides a potential strategy to investigate the mechanisms of IRI and provide better transplant outcomes for clinical practice.

BACKGROUND: Frozen embryo transfer resulted in a higher birthweight and an increased risk of macrosomia than fresh embryo transfer. However, the mechanism was still unclear. When the impact of frozen embryo transfer on fetal growth began was unknown. Crown-rump length at 11–13 weeks had been regarded as a good indicator of fetal growth in the first trimester and had been used for gestational age calculation in women with uncertain last menstrual periods. OBJECTIVE: To evaluate the association between frozen embryo transfer and early fetal growth, particularly the crown-rump length, then fresh embryo transfer. The secondary objective was to investigate the potential correlation between crown-rump length and birthweight. STUDY DESIGN: This was a retrospective cohort study conducted at the Reproductive Medical Center of Shandong University. A total of 4949 patients who obtained singleton pregnancy after frozen embryo transfer and 1793 patients who got singleton pregnancy after fresh embryo transfer between January 1, 2017 and December 31, 2022 were included. The primary outcome was the crown-rump length measured via ultrasound at 11–13 weeks gestation. The secondary outcomes were perinatal outcomes, including birthweight and the risk of large for gestational age, small for gestational age, macrosomia, low birthweight, and premature delivery. Multivariable linear regression models were used to adjust for potential confounders of crown-rump length. RESULTS: A total of 6742 live singleton births after frozen embryo transfer or fresh embryo transfer were included in this study. In the univariable analysis, the frozen embryo transfer group had a larger crown-rump length (5.75±0.53 cm vs 5.57±0.48 cm, P

Background: Food allergy (FA), which is a condition that has no effective cure and can result in severe life-threatening allergic reactions, remains a global public health concern; however, little is known about how FAs are currently managed in the Asia-Pacific region. Objective: The main objective of this survey was to evaluate the epidemiology of FA, as well as the availability of resources and practices for management of FA and anaphylaxis by health care providers across Asia. Methods: From June 2022 to September 2022, a questionnaire-based survey comprising 66 questions was electronically sent to member societies of the Asia Pacific Association of Allergy Asthma and Clinical Immunology by using Survey Monkey. Results: A total of 20 responses were received from 15 member countries and territories. Compared with the pediatric data, there was a lack of prevalence data for FA in adults. Except for Australia and Japan, most regions had between 0.1 and 0.5 allergists per 100,000 population and some had fewer than 0.1 allergists per 100,000 population. The perceived rate of FA in regions with a short supply of allergists was high. Although specific IgE tests and oral food challenges were available in all regions, the median wait time for oral food challenges at government facilities was 37 days (interquartile range = 10.5-60 days). Seven regions still relied on prescriptions of ampules and syringes of injectable adrenaline, and adrenaline autoinjectors were not accessible in 4 regions. Oral immunotherapy as FA treatment was available in half of the surveyed countries and territories. Conclusions: Our study offers a cross-sectional evaluation of the management practices for FA in each Asia Pacific Association of Allergy Asthma and Clinical Immunology member country or territory. Urgent actions are required to enhance allergy services, improve the accessibility and affordability of adrenaline autoinjectors, and conduct robust epidemiologic studies.

Background:. Sexual health is critical to overall health, yet sexual history taking is challenging. LGBTQ+ patients face additional barriers due to cis/heteronormativity from the medical system. We aimed to develop and pilot test a novel sexual history questionnaire called the Sexual Health Intake (SHI) form for patients of diverse genders and sexualities. Methods:. The SHI comprises four pictogram-based questions about sexual contact at the mouth, anus, vaginal canal, and penis. We enrolled 100 sexually active, English-speaking adults from a gender-affirming surgery clinic and urology clinic from November 2022 to April 2023. All surveys were completed in the office. Patients also answered five feedback questions and 15 questions from the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction (PROMIS-SexFS) survey as a validated comparator. Results:. One hundred patients aged 19–86 years representing an array of racial/ethnic groups, gender identities, and sexuality completed the study. Forms of sexual contact varied widely and included all possible combinations asked by the SHI. Feedback questions were answered favorably in domains of clinical utility, inclusiveness of identity and anatomy, and comprehensiveness of forms of sexual behavior. The SHI captured more positive responses than PROMIS-SexFS in corresponding questions about specific types of sexual activity. The SHI also asks about forms of sexual contact that are not addressed by PROMIS-SexFS, such as penis-to-clitoris. Conclusions:. SHI is an inclusive, patient-directed tool to aid sexual history taking without cisnormative or heteronormative biases. The form was well received by a diverse group of participants and can be considered for use in the clinical setting.

Community nurses play a key role in providing continuous home care for patients with chronic diseases. However, a perfect system of responsibilities and requirements has not yet been formed, and nurses cannot provide high-quality nursing services for home-based patients. We attempted to construct an index of the scope of practice for community nurses providing home-based transitional care for patients with chronic diseases and to guide nurses in playing an active role in transitional care work. From March to May 2023, 14 representative community nurses from the Shanghai Community Health Service Center were selected for group interviews and 2 rounds of Delphi consultation. A total of 14 valid questionnaires were collected. The authority coefficients were 0.94 and 0.93, and the Kendall coefficients were 0.56 and 0.59 for the 2 rounds of expert consultation ( P

Prothrombin time/international normalized ratio (PT/INR) is related to both antithrombotic effect and risk of bleeding. Its role in the prediction of venous thromboembolism (VTE) recurrence and bleeding for patients with acute VTE who undergo direct oral anticoagulants (DOACs) treatment is unclear, despite previous studies revealed some association between them. The predictive efficiency of INR for VTE recurrence and bleeding were analyzed in a retrospective cohort with VTE patients who underwent DOACs treatment. Then its predictive efficiency for VTE recurrence and bleeding were validated in a prospective cohort with the acquired cutoffs range, and compared with anti-Xa level, DASH and VTE-BLEED scores. In the retrospective cohort ( n = 1083), the sensitivity and specificity of INR for the prediction of VTE recurrence were 79.4% and 92.8%, respectively. The area under the curve (AUC) was 0.881 (0.803-0.960)( P = .025). The cutoff value of INR was 0.9. The sensitivity and specificity of INR for the prediction of bleeding were 85.7% and 77.9%, respectively. The AUC was 0.876 (0.786-0.967)( P 2.1)( n = 34) groups, respectively. The baseline PT/INR value at the initiation of DOACs treatment is an independent predictor for VTE recurrence and bleeding in patients with acute VTE who undergo DOACs treatment.

Background: Recent randomized control trials (JCOG0802 and CALGB140503) have shown sublobar resection to be noninferior to lobectomy for non–small cell lung cancer (NSCLC) ≤2.0 cm. We have previously proposed histologic criteria stratifying lung adenocarcinoma into indolent low malignant potential (LMP) and aggressive angioinvasive adenocarcinomas, resulting in better prognostication than provided by World Health Organization grade. Here we determine whether pathologic classification is reproducible and whether subsets of adenocarcinomas predict worse outcomes when treated by wedge resection compared to lobectomy. Methods: A retrospective cohort of 108 recipients of wedge resection and 187 recipients of lobectomy for stage I/0 lung adenocarcinomas ≤2.0 cm was assembled from 2 institutions. All tumors were classified by a single pathologist, and interobserver reproducibility was assessed in a subset (n = 92) by 5 pathologists. Results: Angioinvasive adenocarcinoma (21%-27% of cases) was associated with worse outcomes when treated with wedge resection compared to lobectomy (5-year recurrence-free survival, 57% vs 85% [P = .007]; 5-year disease-free survival [DSS], 70% vs 90% [P = .043]; 7-year overall survival, 37% vs 58% [P = .143]). Adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and LMP exhibited 100% 5-year DSS regardless of the surgical approach. Multivariable analysis showed that angioinvasion, tumor size, margin status, and extent of nodal sampling were significantly associated with recurrence but not with surgical procedure. There was substantial interobserver reproducibility among the pathologists for the diagnosis of angioinvasive adenocarcinoma (κ = 0.71) and the combined indolent AIS/MIA/LMP group (κ = 0.74). Conclusions: The majority (∼75%) of lung adenocarcinomas ≤2 cm are adequately managed with wedge resection; however, angioinvasive adenocarcinomas (∼25%) treated by wedge resection with suboptimal nodal sampling exhibit poor outcomes, with a 40% to 45% rate of recurrence within 5 years and 60% to 65% overall mortality at 7 years.

Objective: To assess prevalence, clinical characteristics, and risk factors associated with low flow state (LFS) in a multiethnic population with normal left ventricular ejection fraction (LVEF). Patients and Methods: The study included 4398 asymptomatic participants undergoing cardiac magnetic resonance from July 17, 2000, to August 29, 2002. Left ventricular (LV) mass, volume, and myocardial contraction fraction were assessed. Low flow state was defined as stroke volume index (SVi of

Background: Bone metastasis is frequently common in advanced lung cancer with the major issue of a pathological fracture. Previous studies suggested that Astragalus membranaceus (Qi) and Ampelopsis japonica (Lian), which are used as folk medicine in China, have potential effects on inhibiting tumor growth and protecting bones, respectively. In this study, an experiment on the inhibitory effect of the Qilian formula (AAF) in vivo was designed to examine tumor growth in bone and osteoclast formation. Materials and Methods: The bone metastasis xenograft models were established by implanting NCI-H460-luc2 lung cancer cells into the right tibiae bones of mice. After confirming the model’s viability through optical imaging 7 days post-implantation, 2 groups, namely the AAF group and the control group, were administered 0.3 mL of AAF extract (9 g/kg/day) or normal saline via intragastric delivery for a duration of 4 weeks. Throughout the study, we longitudinally assessed tumor burden, bone destruction, and weight-bearing capacity in vivo using reporter gene bioluminescence imaging (BLI), micro-CT, and dynamic weight-bearing (DWB) tests. Mechanistic insights were gained through Hematoxylin-eosin (H&E) staining, immunohistochemical (IHC) analysis, western blotting, and flow cytometry. Results: Qilian formula produced significant inhibition to the progress of bone destruction and tumor burden in the right tibiae bone in the treatment group. It was further evidenced by molecular imaging in vivo via small animal micro-CT and BLI with parametric quantification, characterizing significantly lower uptake of BLI signal in the treated tumor lesions and improving the pathological changes in the microstructure of bone. Furthermore, DWB tests revealed that Qilian formula treatment significantly maintained the weight-bearing capacity. According to immunohistochemical analysis, the effect of the Qilian formula appeared to involve the suppression of osteoclast formation by lower expression of the tartrate-resistant acid phosphatase. Cell apoptosis and death induction were evidenced by a higher percentage of Bal2、BAX and caspase 3 expressions of Qilian formula-treated tumor tissues. Conclusions: Our study demonstrated a significant inhibitory effect of the Qilian formula on the progression of osteolytic invasion in vivo by suppressing osteoclastogenesis and promoting apoptotic cell death.

Background: Soothing the liver (called Shu Gan Jie Yu in Chinese, SGJY) is a significant therapeutic method for breast cancer in TCM. In this study, 3 liver-soothing herbs, including Cyperus rotundus L., Citrus medica L. var. sarcodactylis Swingle and Rosa rugosa Thunb. were selected and combined to form a SGJY herbal combinatory. The Aim of the Study: To investigate the inhibiting effect of SGJY on breast cancer in vivo and vitro, and to explore the potential mechanisms. Materials and Methods: SGJY herbal combination was extracted using water. A breast cancer rat model was developed by chemical DMBA by gavage, then treated with SGJY for 11 weeks. The tumor tissue was preserved for RNA sequencing and analyzed by IPA software. The inhibition effects of SGJY on MCF-7 and T47D breast cancer cells were investigated by SRB assay and cell apoptosis analysis, and the protein expression levels of SNCG, ER-α, p -AKT and p -ERK were measured by western blotting. Results: SGJY significantly reduced the tumor weight and volume, and the level of estradiol in serum. The results of IPA analysis reveal SGJY upregulated 7 canonical pathways and downregulated 16 canonical pathways. Estrogen receptor signaling was the key canonical pathway with 9 genes downregulated. The results of upstream regulator analysis reveal beta-estradiol was the central target; the upstream regulator network scheme showed that 86 genes could affect the expression of the beta-estradiol, including SNCG, CCL21 and MB. Additionally, SGJY was verified to significantly alter the expression of SNCG mRNA, CCL21 mRNA and MB mRNA which was consistent with the data of RNA-Seq. The inhibition effects of SGJY exhibited a dose-dependent response. The apoptosis rates of MCF7 and T47D cells were upregulated. The protein expression of SNCG, ER-α, p -AKT and p -ERK were all significantly decreased by SGJY on MCF-7 and T47D cells. Conclusion: The results demonstrate that SGJY may inhibit the growth of breast cancer. The mechanism might involve downregulating the level of serum estradiol, and suppressing the protein expression in the SNCG/ER-α/AKT-ERK pathway.

MET protooncogene (MET) alterations are known driver oncogenes in NSCLC. Since the identification of MET as a potential therapeutic target, extensive clinical trials have been performed. As a result, MET-targeted therapies, including MET tyrosine kinase inhibitors, monoclonal antibodies, and MET antibody–drug conjugates now play important roles in the standard treatment of MET-altered NSCLC; they have considerably improved the outcomes of patients with tumors that harbor MET oncogenic drivers. Although clinical agents are currently available and numerous other options are in development, particular challenges in the field require attention. For example, the therapeutic efficacy of each drug remains unsatisfactory, and concomitantly, the resistance mechanisms are not fully understood. Thus, there is an urgent need for optimal drug sequencing and combinations, along with a thorough understanding of treatment resistance. In this review, we describe the current landscape of pertinent clinical trials focusing on MET-targeted strategies and discuss future developmental directions in this rapidly expanding field.